A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression
Abstract Background Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a r...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01471-w |
| _version_ | 1818228594097258496 |
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| author | Lingli Luo Min Wang Xianping Li Can Luo Shan Tan Sheng Yin Lei Liu Xiaolin Zhu |
| author_facet | Lingli Luo Min Wang Xianping Li Can Luo Shan Tan Sheng Yin Lei Liu Xiaolin Zhu |
| author_sort | Lingli Luo |
| collection | DOAJ |
| description | Abstract Background Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated. Methods Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2‐AS1 or SMAD3 and miR‐143‐3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis. Results ACTA2-AS1 was significantly increased in CC tissues and cells and miR‐143‐3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells. Conclusions In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC. |
| first_indexed | 2024-12-12T10:05:11Z |
| format | Article |
| id | doaj.art-4b1d736d761648519aed2d48b977e53d |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-12T10:05:11Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-4b1d736d761648519aed2d48b977e53d2022-12-22T00:27:53ZengBMCCancer Cell International1475-28672020-08-0120111310.1186/s12935-020-01471-wA novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expressionLingli Luo0Min Wang1Xianping Li2Can Luo3Shan Tan4Sheng Yin5Lei Liu6Xiaolin Zhu7Department of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South UniversityAbstract Background Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated. Methods Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2‐AS1 or SMAD3 and miR‐143‐3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis. Results ACTA2-AS1 was significantly increased in CC tissues and cells and miR‐143‐3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells. Conclusions In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.http://link.springer.com/article/10.1186/s12935-020-01471-wCervical cancerACTA2-AS1miR-143-3pSMAD3ceRNA |
| spellingShingle | Lingli Luo Min Wang Xianping Li Can Luo Shan Tan Sheng Yin Lei Liu Xiaolin Zhu A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression Cancer Cell International Cervical cancer ACTA2-AS1 miR-143-3p SMAD3 ceRNA |
| title | A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression |
| title_full | A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression |
| title_fullStr | A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression |
| title_full_unstemmed | A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression |
| title_short | A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression |
| title_sort | novel mechanism by which acta2 as1 promotes cervical cancer progression acting as a cerna of mir 143 3p to regulate smad3 expression |
| topic | Cervical cancer ACTA2-AS1 miR-143-3p SMAD3 ceRNA |
| url | http://link.springer.com/article/10.1186/s12935-020-01471-w |
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